Our previous prospective studies have shown that elevated chronic stress in the child's family environment leads to increased numbers of illnesses and febrile illnesses for the child, enhanced natural killer (NK) cell function and TNF-1 cytokine production, and increased percentages of CD8+ effector memory cells suggesting poor immunological control of CMV. We hypothesize that child stress leads to enhanced production of critical cytokine(s) with subsequent impairment of adaptive immune responses, and that these effects are responsible for an increased susceptibility to infectious diseases and an increase in the number of common infections leading to illnesses. The proposed study builds on and extends previous work in several ways. We aim to determine how stress in the child's familial and social context leads to an increased frequency of illness in the child. We will also determine the types of illnesses impacting children's health and better define the immune changes that mediate the adverse effects of stress on health. We will pursue these aims in a prospective, longitudinal study of 178 racially and socio-economically diverse children from 10 to 13 years of age. Our evaluations will include repeated standardized assessments of six domains of child stress including parent-child relationships, parent psychiatric symptoms, family conflict, neighborhood factors, stressful life events, and peer relationships. Protective features of each of these domains will also be measured. Additionally, we will employ a rigorous observational method to study the quality of the parent-child relationship. We hypothesize that poor parent-child relationship quality will mediate the relationships between family stress and increased rates of illnesses in children. Furthermore, we hypothesize that child stress and parent child relationship quality will negatively impact adaptive immune responses to vaccine challenge. And these changes in immune function will mediate the effects of stress on health. Our immunological investigations will focus on antigen specific immune responses to the newly introduced meningococcal conjugate vaccine in children. We will measure specific antibody titers to each meningococcal serogroup by ELISA as well as CD4+ and B cell memory responses by Elispot assays at 1, 3, and 6 months following vaccination to determine the magnitude of the initial immune response. We will also measure IL-6 and TNF-1 cytokine levels following immunization. At one and two years following vaccination antibody titers, cytokine levels, and CD4+ and B cell memory responses will be repeated to detect differences in the rate of decline. The psychological and immunological investigations will be complemented by a rigorous and objective documentation of illnesses and febrile illnesses to begin to precisely define the effects of stress in the parent-child system on immune function and health. Our long-term goal is to identify mechanisms linking family stress to children's health that are potentially modifiable through intervention. PUBLIC HEALTH RELEVANCE: The goal of this study is to uncover the ways whereby family and child stress lead to more illnesses for children. We will also look for links between stress and children's immune system function that may lead to child illness. Finding these links will allow us to create programs to modify the effects of stress on health.